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Sodium Homeostasis. Sodium is an electrolyte of major importance in the human body. It is necessary for : normal extracellular volume dynamics Na in ECF volume contraction . Na in ECF edema . excitability of certain tissues
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Sodium Homeostasis • Sodium is an electrolyte of major importance in the human body. It is necessary for : • normal extracellular volume dynamics • Na in ECF volume contraction. Na in ECF edema. • excitability of certain tissues • cotransport and counter transport…glucose, a.a, H+ • concentration of urine in thick ascending • Sodium accounts for a significant portion of plasma osmolarity. The latter can be estimated by multiplying plasma sodium concentration times 2.1. Most of the primary active transport in the entire tubular system is to transport Na+
7 % (16,614 mEq/day) 65 % (1789 mEq/d) 25,560 mEq/d 25 % (6390 mEq/d) 2.4% (617 mEq/d) 0.6 % (150 mEq/d) Normal Renal Tubular Na+ Reabsorption
Sodium Homeostasis • Sodium balance is achieved when intake and output equal each other. • Sodium intake is about 120-155 mmol/d in the average American diet (≈ 4 gm). Logically, the daily output would be 120-155mmol/d as well. • The kidney accounts for 115-150 mmol of this output. Hence, the kidney is a major organ in sodium homeostasis.
Na Clearence • Sodium clearance can be calculated as follows: • UNa+ = 150mmol/d ÷ 1.5l/d urine per day = 100mmol/l • CNa+ = (UNa+ / PNa+) * V = (100 / 145) * 1 = 0.69ml/min • Notice that the value is less than 1 ml/min, which indicates that sodium is mostly reabsorbed. • Sodium reabsorption is rather extensive. In order to appreciate this, let’s do the math. • Amount of sodium filtered per day = 180l/d * 140mM = 25200mEq • Amount of sodium excreted by the kidney = 150 mM • Percent reabsorbed = 25050 / 25200 = 99.4%
sodium homeostasis • Three factors are principally involved in sodium homeostasis: • GFR(1st factor) • Aldosterone (2nd factor) • Atrial natriuretic peptide (3rd factor)
CNa+ = [UNa+ /PNa+] x V = 100/140 x 1 = < 1 ml/min 125 ml/min Flow rate <1ml/min Prox desc asc distal coll.duct
about the curve : 1. the decrement in the flow rate (F.R) throughout the kidney tubules . 2. F.R remains relatively constant at the level of the ascending limb of Henle .
There are 2 ways to handle Na+ in the kidney : 1) Through filtration (↑or↓) or 2) Reabsorption • Example: when Na+ intake is increased: • ↑Na+ filtered ↑reabsorption in the proximal… This is called " glomerulotubular balance " to ensure that a constant fraction is reabsorbed ( ≈ 2/3 ) this occurs in the proximal tubules • In distal tubule Na+ reabsorption is decreased.
A-Reabsorption at proximal tubules • There are2 ways for Na+ transport through the cells: 1. transcellular channels (T-max) 2. paracellular tight junction • in the early proximal tubules, tight junctions are not so tight paracellular route ( + transcellular route ), so transport is NOT T-max dependent it is gradient/time dependent . • ↑Conc ↑ time in prox. tubules more chance to be reabsorbed. • In more distal parts of the nephron , the tight junctions are tighter T-max dependent transport .
A-Reabsorption in proximal tubules • In the early part of the proximal tubule , Na+ & H2O are reabsorbed with glucose & amino acids by "cotransport process". • [Na+]out = 140 mEq • [Na+]in = 14 mEq • So Na+ moves down gradient from the luminal side to the cell, while it is pumped actively through the basolateral membrane (anti-gradient) .
A-Reabsorption in proximal tubules • In the late proximal tubule , Na+ is reabsorbed with Cl- , because in the early prox.tub. , removal of large amounts of Na + with glucose creates negativity inside the lumen. so to get back to normal , Cl- is reabsorbed. Na+ follows Cl-.
B. Reabsorption in descending limb of Henle (no reabsorption). • C. Reabsorption in the Ascending limb of Henle. reabsorption involves ( Na+-K+-2Cl- ) co-transporter without H2O , this is called [single effect] ↑ osmolarity in the interstitium and ↓ osmolarity in the TF.
Clinical point 1. Furesamide ( Lasix): a potent loop diuretic acts on the thick ascending limb of Henle TAL where it inhibits Na-2Cl-K ↑ Na+ Excretion. Lasix is used in pulmonary edema & hypertension. 2. Thiazide/Chlorothiazide(moderate diuretic) acts on distal convoluted tubule DCT inhibiting Na/Cl reabsorption • Those 2 diuretics are called [potassium-wasting diuretics]…they induce hypokalemia
Reabsorption of Na+ • D. Reabsorption in late distal tubules & cortical collecting duct. • Reaborption of Na+ & secretion of K+ occur through the principal cells.
Clinical point • 1. Spironolactone (aldactone): works on principal cells by decreasing K+ secretion aldactone diuretics are called [K+ sparing diuretics] or [aldosterone antagonists]. • 2. Osmotic diuretics , (ex: Mannitol) is a glomerular marker & has an osmotic effect i.e. it's not reabsorbed so it drives H2O with it , used in brain edema .
Control of Na++ • when Na+ intake is increased increase in GFR through increasing ECV and BP. When ECV increases π in peritubular capillary decreases due to dilution
Control of Na+ • How does the body control increase in Na+ intake ? • Altering GFR • Altering Reabsorption • 1-Altering GFR: • When Na+ intake increases Glomerulotubular feedback does not work for unknown reason increase Na+ Excretion. • increase Na+ intake increase Pa increase GFR (Pressure Natriuresis)
Control of Na 2-Altering reabsorption: When Na+ intake increases the RFC is shifted to the left to ensure increase Na+ excretion. This shift means less production of AIIwhich results in less Na+reabsorption and thus increase its excretion. In addition less AII means less aldosterone and less Na+ reabsorption. • Aldosterone is also autoregulated….means whenever [Na+] in plasma increases, Aldosterone production decreases • ANP (Atrial Natriuretic Peptide) increases due to atrial pressure 1. Afferent Arterial dilatation. 2. inhibit adrenal cortex decrease aldosterone production.
Diuretics • They are actually 7 groups each work on a specific cell and with a different mechanism. • some of these groups are used for specific indications like carbonic anhydrase inhibitors which is used in glaucoma • hypokalemia is a serious complication of loop diuretics and thiazide